Method for producing peroral capsules



J1me 1965 .1. A. GLASSMAN 3,186,910

METHOD FOR PRODUCING PERORAL CAPSULES Filed March 8, 1962 2 Sheets-Sheet 1 .1; ne -r June 1965 J. A. GLASSMAN 3,186,910

METHOD FOR PRODUCING PERORAL CAPSULES Filed March 8, 1962 2 Sheets-Sheet 2 &

48 INVENTOR.

Jacafifi. Glass/ em United States Patent 3,2863% METHQE 1 8R PRODUCING PERQRAL CAESULES Jacob A. Glassman, 1689 Meridian Ave, Miami Beach, Fla. Filed Mar. 8, 1962, Ser. No. 173,474 9 Claims. (Cl. 167-83) This invention relates to improvements in multicompartmented peroral capsules and to the apparatus for and method of making same.

More particularly, the capsules of the present invention are comprised of two or more capsular bodies of conventional construction and which are telcscoped one into the other by use of a conventional type of capsulating machine. The free end portions of the telescopcd body portions are, if necessary, cut ofif or otherwise removed to provide a capsular body having a pair or" compartments separated by a septum and each opening onto an opposite end of body so as to eceive thereover a conventional cap after the required medicament or drug component has been placed in the capped compartment. As an alternative, a portion of the capsule herein referred to as the H-component may be molded as a single unit.

In some instances it may be advantageous to provide three or more compartments in a single capsule. This may be accomplished by practicing the method herein disclosed and utilization of equipment substantially of the herein disclosed character. In instances where a cornpartmented capsule is used to obtain time-delay or controlled release of the medicaments therein contained, the capsules or any selected part of them may be treated by use of the novel apparatus disclosed which functions to spray and dry selected areas of a capsular component or components with a weak critical formalin solution or alcoholic-formalin solution, such as are disclosed in my co-pending application Serial No. 174,951, filed February 23, 1962.

The use of capsule components of specific solubilities such as gelatin-glycerine capsules, pure gelatin capsules, starch or sugar gelatin capsules and capsules made of various other soluble gelatin combinations serve as excellent housings for medicaments and their use has become quite general. However, attempts to control the release of the medicaments contained in dilferent compartments has not attained the expected high level of adoption primarily because of lack of equipment and apparatus capable of making a compartmented capsule body and one having one or more portions thereof treated in a manner to be resistant to the digestive juices of the stomach and/ or to the alkaline juices of the duodenum. In such manner release of medicaments contained in a multicompartmented capsule can be controlled so as, for exampie, to permit a portion of the multi-compartmented capsule to be dissolved in the stomach, another portion in the duodenum, and a third portion in the ileum.

More particularly, the joining of two capsule bodies into a single multi-cornpartmented H-shaped body is best accomplished by the application of force endwise upon a pair of aligned capsule bodies one of which has its open end positioned to receive therein the closed or rounded end of the companion body. The capsule bodies are conventional and are of like or substantially like diameter and are so arranged and supported during the application of the telescoping force endwise thereon as to cause minute compression, distortion or thinning out of the rounded end of the inner capsule body and minute expansion or thinning out of the wall of the companion capsule part. The telescoping force is such as to cause generation of slightly increased temperature in the capsule walls which facilitates their distortion readily and also functions to cause the telescoped parts to bind one to the Patented June 1, 1%65 other and resist separation as though actually fused. In the present disclosure a binder is used to insure firm bonding of the telescoped parts.

The conventional capsule filling machine is further modified, or has associated with it, novel means to spray coat one or both surfaces of the H-shaped capsule body portion or one or both caps with means to instill in the gelatin itself resistance to dissolution in a given acid level, and to effect rapid air drying of same so as to insure that the medium applied to the gelatin wall is made inefiective and is neutralized at a given time and in this manner control the eflective depth to which the medium has penetrated the gelatin wall.

It is therefore an object of the invention to provide a novel method and pre-assembly of a pair of gelatin capsule body portions into a unitary whole that is substantially devoid of external markings or objectionable protrusion at the joint.

Another object is to provide a novel apparatus for joining capsule bodies and for treating some or all of the walls of said bodies with means to render the treated walls variably resistant to stomach acids and/or to alkaline acids of the duodenum or ileum.

Another object is to provide a capsule body formed of two like body portions telescoped one into the other and in a manner to cause relative displacement of the material of the capsu'e walls to such extent as to cause tight binding of the telescoped areas with minimum distortion.

Another object is to provide novel apparatu for the assembly and treating of capsular components of a multicompartmented per-oral capsule.

Another object is to provide a novelly constructed unitary H-shapcd component for a peroral capsule.

The structure by means of which the above noted and other features and advantages of the invention are attained will be described in the following specification, taken in conjunction with the accompanying drawings, showing preferred illustrative embodiments of the invention, in which:

FIG. 1 is a schematic perspective view of components of encapsulating equipment modified to perform steps of the process of capsule manufacture herein disclosed.

FIG. 2 is an enlarged fragmentary sectional view of the capsule ring and binder applying head associated for performing work on capsule components seated in the capsule ring.

FIG. 3 is a similar sectional view showing the capsule ring having a second capsule head disposed thereover and illustrating preliminary assembly of two capsule components.

FIG. 4 is an enlarged sectional view of an H-shaped capsule component produced in the PEG. 3 equipment and indicating the lines of subsequent cut-oil of the end portions thereof.

H6. 5 is a sectional view of the capsule ring associated with a chemical spray head, and showing the cut-off capsule component of FIG. 4 seated therein.

FIG. 6 is a view similar to FIG. 5 but showing the spray head replaced by an air drying head.

FIG. 7 is a perspective view of the capsule ring showing it associated with filler mechanism.

FIG. 8 is an enlarged detail sectional view of the capsule ring and filler mechanism, showing one end of an H-shaped capsule component previously treated as in F168. 5 and 6, being filled.

FIG. 9 is a detail sectional View similar to FIG. 8, but showing a second H-shaped capsule component telescoped into the filled end of a first H-shaped capsule component.

FIG. 10 is a representative sectional view illustrating the subsequent steps of capping the FIG. 9 subassembly of a 3-compartmented capsule.

areaoro FIG. A is a view showing the steps of assembly of the FIG. 10 disclosure.

FIG. 11 is a longitudinal sectional view of a two compartmented capsule produced by the herein disclosed method and equipment.

FIG. 12 is an enlarged central sectional view of another type of H-shaped capsule component produced in accordance with the herein disclosed method and equipment.

FIG. 13 is a detail sectional view of mold cavities used to produce a one piece H-shaped capsule component.

FIG. 14 is a longitudinal sectional view of an H-shaped capsule component formed in the FIG. 13 mold.

FIG. 15 is a longitudinal sectional view of another H-shaped capsule component.

Reference is made at this time to the representative equipment illustrated in an exemplary form in FIG. 1, and useful in producing in an economical manner selected component parts of the multicompartmented soft gelatin capsules and for filling, interfitting and capping said parts.

Said machine, which is shown in part only, includes a capsule ring 10 having a plurality of sockets 11 in which a part of a soft gelatine capsule 12 (FIG. 2) is seated with its rounded closed end uppermost. As best illustrated in FIG. 2, the closed end of the capsule part 12 extends above the top surface 13 of the capsule ring 11.

The amount of protrusion of the capsule parts 12 above surface 13 may be controlled by adjustment of a floor 14 which affords a support for the ejection plunger 15.

In the present disclosure the exposed part of the capsule is preferably treated with a binder, which may comprise any of the well known binders now generally used in the industry. This binder preferably is applied to all capsule parts in the capsule ring at one time and to accomplish this a binder spray head 16 is swung into position over ring 10. Referring again to FIG. Lthis head 16 preferably is supported on an arm 17 rotatable on or with a support 18 so as to be movable about a horizontal' arc, as indicated by arrow line 19, into and out of position over the capsule ring 10. The arm 17 also preferably includes a swivel 21 that permits head 16 to be swung 180 in instances when. spray is to be applied to a capsule ring (not shown) supported above the head.

The head 16 may be of any practical construction such as shown wherein it carries a conduit 22' for supplying binder to an interior channel 23 thereof for ultimate distribution onto the capsule parts through jet openings 24.

Immediately following application of the binder onto the capsule parts 12, the head 16 is swung about its axis 18 out from over the capsule ring and a second head 25 (FIGS. 1 and 3) carrying component capsule parts 26 is moved into registering alignment with capsule ring 11. This head 25 also is mounted on an arm 27 for movement through a horizontal are about axis 28 and for rotation in a vertical plane about swivel 29. As best shown in FIG. 3, pressurized air is delivered into each recess 30 of head 25 through ports 31 connecting them with a common duct 32 having connection through conduit 33 (FIG. 1) with a source of pressure. When the head 25 is positioned as shown in FIG. 3, air is ejected through ports 31 to project the capsule parts 26 downwardly into telescoped relation one over each related capsule part 12. As perhaps best shown in FIG. 4, the parts 12-26 are of like or substantially like diameters and when the part 26 is forcibly telescoped over part 12, the gelatin of the parts flows slightly butsufiiciently to enable the parts to telescope in the manner shown whereupon they are bonded or fused together by the binder. It is inherent in the assembly that a substantially smooth joint is efiected because of the relative expansion of the outer wall and contraction of theinner wall of the telescoped parts and the thinning out of the material constituting the wall thickness.

Following the joining of the two capsule parts 12 6, the end portion of each part is severed as along lines s-s (FIG. 4) so as to provide a capsule component that is substantially H-shaped in section. This H-shaped capsule component 34' is repositioned in the capsule ring 10 (FIG'S) and the upwardly projecting end portion thereof may be sprayed with a suitable weak formalin solution or alcoholic-formalin solution as described in detail'in my copending application Serial No. 174,951, filed February 23, 1962.

The solution may be applied through jet ports 35 in a head 36 (FIGS. 1-5) which are supplied through inner duct 37 and supply conduit 38. This head, like those previously described, may be pivotally mounted about a vertical axis 28 and may include a swivel 39 to permit it being completely turned over so as to afford application of formalin to a capsule component that might be carried in a capsule ring located above head 36. This chemical treatment of the capsule component'34 or any part'thereof, is optional and is efiected when it is desired to make all or a part of the walls of said component non-susceptible to the action of stomach acids and/or the alkaline juices of the duodenum. In the FIG. 5 disclosure the outside wall of the upper half of component 34 is sprayed and treated and, following such treatment, the sprayed area is quickly dried by warm air ejected from still another head 41 (shown in FIG. 6 only) that may also be mounted like the heads discussed hereinabove. The warm air quickly dries the formalin solution and stops all further reaction with the gelatin consequently, the treated capsule component wall is altered chemically in depth only.

The treated capsule component is now ready to be partly filled as illustrated in FIGS. 7 and 8, which discloses the positioning of the capsule ring 19 beneath a conventional filling apparatus 4-2 and which ring is rotated relative to said apparatus to successively carry all of the capsule components 34- beneath the filling nozzles 43 thereof.

In the event a two compartmented peroral capsule is desired, such as is shown in FIG. 11, a cap 44 may be press-fitted over the filled end A of the I-I-shaped component 34' as by means of the equipment illustrated in FIG. 3. The partly capped cap-sule component 34 is then reversed in its position in capsule ring 11? and the other half B of same is'filled, in the manner shown in FIG. 8, and then capped with a cap 45. Obviously,

either or both caps may be treated with formalin soluquired, a second H-shaped capsule component 46, best shown in FIG, 9, is projected into or over the filled end of A of component 34. This second component 46 may be produced in the same manner as described hereinabove with respect to production of the component'34. Following the assembly of the two H-shaped components, the uppermost compartment C in component 46 is filled with the required medicament and said compartment is capped as by a cap 47, whereupon the position of the capsule is reversed, as shown in FIG. 10, and the unfilled compartment Din the capsule component 34 is filled with a medicament and then closed with a cap 48. The capping is etfected in the same manner as the two compartmented capsule is capped and anyone or both of the caps, as well as the second H-shaped component 46 or any part thereoflmay be subjected to the intermediate step or steps of being treated with the formalin solution as described previously so as to render the peroral capsule suitable for delayed release of at least some of the medicaments therein contained. 7

Mgre specifically, and by way of example, the walls of compartment D may be treated to resist the acids of the stomach and to be slightly resistant to the alkaline acids of the duodenum so as to be dissolved in the ileum and release the contained medicaments at their situs. The walls of compartment C may be treated to resist stomach acids and be soluble in the alkaline acids of the duodenum whereas the walls of the remaining compartment A may be left untreated so that said walls will dissolve and release the contained medicaments in the stomach.

It should be apparent that applicant has disclosed a novel method and means for making a time-delay release peroral capsule and one that can be effected without involving the production or use of expensive equipment inasmuch as existing capsulating equipment can, with slight modification, be adapted to perform the requisite steps of manufacturing, filling, treating and assembly.

The herein disclosed assembly atfords means whereby selected capsule components may be filled and combined with other selected capsule components. This is illustrated in FIG. A, Where capsule component -34 has compartment D filled with a selected medicament or combination of medicaments and carried in an upper capsule ring 25. The companion component 46 has its compartment C filled with medicament, capped and arranged in lower capsule ring 10. The medial compartment may be then filled with a desired medicament and the two components assembled as illustrated in FIG. 10. In this manner any desired combination of medicaments may be made up by the selection of pre-filled components 3446 and subsequently adding a third medicament in the medial compartment regardless of any existing incompatibilities.

As an alternate structure for the H-shaped capsule component, applicant proposes to mold same in a special mold. This is illustrated in one embodiment in FIGS. 13 and 14. As shown, in the H-shaped component 5h which comprises two medicament compartments E and F separated by septum 51, is formed in heated molds 52-53 having cavities in the form of cylinders 54-55, respectively, into which a mass of gelatin 56 is flowed during the pressure molding thereof.

In the FIG. 12 disclosure, the H-shaped capsule component 57 is made up of a pair of like capsule parts 5859 one of which has its inside peripheral edge chamfered, as at 61, to have surface abutment with the rounded end 62 of the companion capsule part 58. A binder is employed to bond the two together after they have been telescopically mated as shown, and their outer end portions are severed as on line s-s to provide the requisite compartment capacity.

The H-shaped capsule component 63 shown in FIG. 15, is constructed of two flat bottom capsule parts 63a and 6312, which are brought together as shown and secured as by a binder into a single unit. Heat or moisture may be used to effect the bonding. The unit is subsequently coated with a thin layer 64 of gelatin, trimmed along line ss and, if desired, treated in whole or in part with formalin solution.

Although several embodiments of the invention have been disclosed in the accompanying drawings and described hereinabove, it should be understood that the various steps recited may be performed in any desired sequence and altered to suit various requirements and may be made in equipment other than that illustrated, the disclosure of which is exemplary and not restrictive, and that applicant does not desire the invention to be restricted to the precise recitations herein but only by the scope and spirit of the appended claims.

Having described the invention, what I claim and desire to secure by Letters Patent of the United States is:

1. The steps in the production of .a multi-compartmented peroral capsule which consists of telescoping the closed end of a tubular capsule part into the open end of. a like tubular capsule part under such conditions as to cause the material of the telescoped portions thereof to flow in a manner to provide a substantially smooth exterior surface at the joint, bonding said telescoped portions one to the other, severing the free end portions of said assembled parts to provide an H-shaped capsule component, treating at least a part of said component to render the treated part resistant to acids in the stomach, filling one end portion of said component with a medicament, capping said end, filling the other end portion of said component with a medicament, capping said last named end, and finally treating the cap on the treated portion of said component to render it resistant to acids in the stomach.

2. The steps in the manufacture of an H-shaped gelatin capsule component which comprises placing a gelatin tubular capsule part closed at one end in a capsule ring with the closed end protruding therefrom, applying a binder to said protruding end, telescoping a gelatin capsule part of substantially the same diameter over the protruding end of the first named capsule part, and finally trimming the free oppose-d ends of said parts.

3. The improvement in the art of manufacturing gelatin capsule components by machinery which consists in telescoping two like cylindrical capsule parts under applied pressure endwise one into the other and bonding same into a unitary structure.

4. The improvement in the art of manufacturing gelatin capsule components by machinery which consists in telescoping two like cylindrical capsule parts under applied pressure endwise one into the other, bonding same into a unitary seamless structure, and subsequently trimming the opposed free ends of the structure.

5. The improvement in the art of manufacturing gelatin capsule components by machinery which consists in telescoping two like cylindrical capsule parts under applied pressure endwise one into the other, bonding same int-o a unitary structure, trimming the opposed free ends of the capsule parts, and treating the walls of at least one part of said structure with a medium to render it non-susceptible to the acids of the stomach.

6. The improvement in the art of manufacturing a mul-ti-cornpa-rtmented medicament containing gelatin capsule by machinery which consists of telescoping two substantially identical cylindrical capsule parts under applied pressure endwise one into the other and bonding the telescoped portions of the parts together, trimming the joined capsule par-ts to provide compartments there-in of predetermined capacity and opening onto opposite ends of the assembled parts, treating the walls of at least one of said compartments with a medium to render it non-soluble in the acids of the stomach, filling one of said compartments with a medicament, capping said filled compartment with a gelatin cap, filling the other compartment with a medicament, capping said other compartment, and then treating the cap on the treated capsule part to render it non-soluble in the acids of the stomach.

7. The improvement in the art of manufacturing a gel tin capsule component by machinery which consists in tel scoping two cylindrical capsule parts of substantially like diameters under pressure endwise one into the other, and wherein the telescoped end of one of said parts is substantially spherical and the telescoping end of the other part is chamfered.

8. The improvement in the art of manufacturing a gelatin capsule component by machinery which consists in telescoping two cylindrical capsule parts of substantially like diameters under pressure endwise one into the other and wherein the telesc-oped end of one of said parts is substantially spherical and the telescoping end of the other part is chamfered, and applying a binder to the telescoped surface of at least one part prior to assembly.

9. The improvement in the art of manufacturing an H-shaped gelatin capsule component which consists in carrying the closed ends of two capsule parts into surface engagement, bonding the abutting surfaces into a unitary structure, and applying a layer of gelatin-e over the exterior surfaces of said structure.

(References on following page) References Cited in the file of this patent UNITED STATES PATENTS Zipper Jan. 25, 1944 Fox Dec. 4, 1945 Thompson Apr. 22, 1952 Lawrence et a1; Dec. 8, 1953 Greer et a1. June 16, 1959 De Boer Jan. 1, 1963 Cooke Q. 'Mar. 12, 1963 

1. THE STEPS IN THE PRODUCTION OF A MULTI-COMPARTMENTED PERORAL CAPSULE WHICH CONSISTS OF TELESCOPING THE CLOSED END OF A TUBULAR CAPSULE PART INTO THE OPEN END OF A LIKE TUBULAR CAPSULE PART UNDER SUCH CONDITIONS AS TO CAUSE THE MATERIAL OF THE TELESCOPED PORTIONS THEREOF TO FLOW IN A MANNER TO PROVIDE A SUBSTANTIALLY SMOOTH EXTERIOR SURFACE AT THE JOINT, BONDING SAID TELESCOPED PORTIONS ONE TO THE OTHER, SEVERING THE FREE END PORTIONS OF SAID ASSEMBLED PARTS TO PROVIDE AN H-SHAPED CAPSULE COMPONENT, TREATING AT LEAST A PART OF SAID COMPONENT TO RENDER THE TREATED PART RESISTANT TO ACIDS IN THE STOMACH, FILLING ONE END PORTION OF SAID COMPONENT WITH A MEDICAMENT, CAPPING SAID END, FILLING THE OTHER END PORTION OF SAID COMPONENT WITH A MEDICAMENT, CAPPING SAID LAST NAMED END, AND FINALLY TREATING THE CAP ON THE TREATED PORTION OF SAID COMPONENT TO RENDER IT RESISTANT TO ACIDS IN THE STOMACH. 